Study to Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

A Phase II, Single-blind, Randomized, Placebo-controlled Trial to Study the Efficacy and Safety of Anti-von Willebrand Factor Nanobody Administered as Adjunctive Treatment to Patients With Acquired Thrombotic Thrombocytopenic Purpura

This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP.

Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).

Inclusion Criteria:

• 18 years of age or older (adults) or aged 12 to < 18 years (adolescents)
• Male or female subject, willing to accept an acceptable contraceptive regimen
• Subject with a clinical diagnosis of TTP
• Requiring PE (one single PE session prior to randomization into the study was allowed)
• Subject accessible to follow-up
• Subject able to provide signed and dated informed consent and assent (if applicable, for adolescents)

Exclusion Criteria:

• Platelet count ≥ 100,000/µL

• Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)

• Clinical evidence of enteric infection with Escherichia coli 0157 or related organism

• Anti-phospholipid syndrome

• Diagnosis of disseminated intravascular coagulation (DIC)

• Pregnancy or breast-feeding

• Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy

• Known with congenital TTP

• Active bleeding or high risk of bleeding

• Uncontrolled arterial hypertension

• Known chronic treatment with anticoagulant treatment that cannot be stopped safely, including but not limited to:

  • vitamin K antagonists
  • heparin or low molecular weight heparin (LMWH)
  • non-acetyl salicylic acid non-steroidal anti-inflammatory molecules

• Severe or life threatening clinical condition other than TTP that would impair participation in the study

• Subjects with malignancies resulting in a life expectation of less than 3 months

• Subjects with known or suspected bone marrow carcinosis

• Subjects who cannot comply with study protocol requirements and procedures

• Known hypersensitivity to the active substance or to excipients of the study drug

• Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows:

  • bilirubin > 3 x upper limit of normal (ULN) (needed to differentiate isolated increase in indirect bilirubin due to hemolysis, this was not an exclusion parameter but disease-related)
  • alanine transaminase (ALT)/ aspartate transaminase (AST) > 5 x ULN
  • alkaline phosphatase (ALP) > 5 x ULN
  • gamma-glutamyl transpeptidase (GGT) > 5 x ULN

• Severe chronic renal impairment, as defined by glomerular filtration rate < 30 mL/min

Note that the use of another investigational drug or device within 30 days prior to screening was not allowed. Participation in non-interventional/observational studies and registries during the study period was allowed. Participation in another clinical study was not allowed until the end of the follow-up period or within 30 days after the last study treatment in case of early subject withdrawal from the study. Subjects who had already participated in the current study and had either completed the study per protocol or had discontinued prematurely, were not allowed to be re-included.